Enantioselective Synthesis of Chiral alpha-Thio-Quaternary Stereogenic Centers via Phase-Transfer-Catalyzed alpha-Alkylation of alpha-Acylthiomalonates

Abstract

An efficient synthetic method for establishing chiral alpha-thio-alpha-quaternary stereogenic center was successfully developed. The enantioselective a-alkylation of alpha-acylthiomalonates under phase-transfer catalytic conditions [50% aq. KOH, toluene, 20 degrees C, and (S,S)-3,4,5-trifluorophenyl-NAS bromide] provided the corresponding alpha-acylthio-alpha-alkylmalonates in high chemical yields (up to 99%) and high optical yields (up to 98% ee).